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• Journal article
  De Simone A, Dhulesia A, Soldi G, Vendruscolo M, Hsu S-TD, Chiti F, Dobson CMet al., 2011,
  , PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol: 108, Pages: 21057-21062, ISSN: 0027-8424
  • Cite
  • Citations: 64
• Journal article
  Mikkelsen H, McMullan R, Filloux A, 2011,
  , PLoS ONE, Vol: 6, ISSN: 1932-6203

  Pseudomonas aeruginosa is a pathogen that causes acute and chronic infections in a variety of hosts. The pathogenic potential of P. aeruginosa is strain-dependent. PA14 is a highly virulent strain that causes disease in a wide range of organisms, whereas PAO1 is moderately virulent. Although PA14 carries pathogenicity islands that are absent in PAO1, the presence or absence of specific gene clusters is not predictive of virulence. Here, we show that the virulent strain PA14 has an acquired mutation in the ladS gene. This mutation has a deleterious impact on biofilm, while it results in elevated type III secretion system (T3SS) activity and increased cytotoxicity towards mammalian cells. These phenotypes can be reverted by repairing the ladS mutation on the PA14 genome. The RetS/LadS/GacS signaling cascade is associated with virulence and the switch between acute and chronic infections. RetS is a sensor that down-regulates biofilm formation and up-regulates the T3SS. Mutations in retS are acquired in strains isolated from chronically infected cystic fibrosis patients and lead to hyperbiofilm formation and reduced cytotoxicity. Conversely, the LadS sensor promotes biofilm formation and represses the T3SS. We conclude that the ladS mutation is partly responsible for the high cytotoxicity of PA14, and our findings corroborate the central role of RetS and LadS in the switch between acute and chronic infections. Given the extensive use of the reference strain PA14 in infection and virulence models, the bias caused by the ladS mutation on the observed phenotypes will be crucial to consider in future research.

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• Journal article
  Joshi A, Coelho MB, Kotik-Kogan O, Simpson PJ, Matthews SJ, Smith CW, Curry Set al., 2011,
  , Structure, Vol: 19, Pages: 1816-1825

  The polypyrimidine tract-binding protein (PTB) is an important regulator of alternative splicing. PTB-regulated splicing of α-tropomyosin is enhanced by Raver1, a protein with four PTB-Raver1 interacting motifs (PRIs) that bind to the helical face of the second RNA recognition motif (RRM2) in PTB. We present the crystal structures of RRM2 in complex with PRI3 and PRI4 from Raver1, which--along with structure-based mutagenesis--reveal the molecular basis of their differential binding. High-affinity binding by Raver1 PRI3 involves shape-matched apolar contacts complemented by specific hydrogen bonds, a new variant of an established mode of peptide-RRM interaction. Our results refine the sequence of the PRI motif and place important structural constraints on functional models of PTB-Raver1 interactions. Our analysis indicates that the observed Raver1-PTB interaction is a general mode of binding that applies to Raver1 complexes with PTB paralogues such as nPTB and to complexes of Raver2 with PTB.

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• Journal article
  Moscoso JA, Mikkelsen H, Heeb S, Williams P, Filloux Aet al., 2011,
  , ENVIRONMENTAL MICROBIOLOGY, Vol: 13, Pages: 3128-3138, ISSN: 1462-2912
  • Cite
  • Citations: 219
• Journal article
  Jamal SM, Ferrari G, Ahmed S, Normann P, Curry S, Belsham GJet al., 2011,
  , JOURNAL OF GENERAL VIROLOGY, Vol: 92, Pages: 2849-2864, ISSN: 0022-1317
  • Cite
  • Citations: 48
• Journal article
  Hideg E, Deak Z, Hakala-Yatkin M, Karonen M, Rutherford AW, Tyystjarvi E, Vass I, Krieger-Liszkay Aet al., 2011,
  , BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS, Vol: 1807, Pages: 1658-1661, ISSN: 0005-2728
  • Cite
  • Citations: 45
• Journal article
  De Simone A, Montalvao RW, Vendruscolo M, 2011,
  , JOURNAL OF CHEMICAL THEORY AND COMPUTATION, Vol: 7, Pages: 4189-4195, ISSN: 1549-9618
  • Cite
  • Citations: 35
• Journal article
  Lossi NS, Dajani R, Freemont P, Filloux Aet al., 2011,
  , MICROBIOLOGY-SGM, Vol: 157, Pages: 3292-3305, ISSN: 1350-0872
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  • Citations: 42
• Journal article
  Fitzpatrick AE, Lincoln CN, van Wilderen LJ, van Thor JJet al., 2011,

  Pump-Dump-Probe and Pump-Repump-Probe Ultrafast Spectroscopy Resolves Cross Section of an Early Ground State Intermediate and Stimulated Emission in the Photoreactions of the Pr Ground State of the Cyanobacterial Phytochrome Cph1.

  , The Journal of Physical Chemistry B

  The primary photoreactions of the red absorbing ground state (Pr) of the cyanobacterial phytochrome Cph1 from Synechocystis PC 6803 involve C15=C16 Z-E photoisomerisation of its phycocyanobilin chromophore. The first observable ground state intermediate in pump-probe measurements of the photocycle, 'Lumi-R', is formed with picosecond kinetics, and involves excited state decay reactions that have 3 and 14 ps time constants. Here, we have studied the photochemical formation of the Lumi-R intermediate using multi pulse picosecond visible spectroscopy. Pump-dump-probe (PDP) and pump-repump-probe (PRP) experiments were carried out by employing two femtosecond visible pulses with 1, 14 and 160 ps delays, together with a broadband dispersive visible probe. The time delays between the two excitation pulses have been selected to allow interaction with the dominant (3 and 14 ps) kinetic phases of Lumi-R formation. The frequency dependence of the PDP and PRP amplitudes was investigated at 620 nm, 640 nm, 660 nm and 680 nm, covering excited state absorption (λmax = 620 nm), ground state absorption (λmax = 660 nm) and stimulated emission (λmax = 680 nm) cross sections. Experimental double difference transient absorbance signals (∆∆OD), from the PDP and PRP measurements required corrections to remove contributions from ground state repumping. The sensitivity of the resulting ∆∆OD signals was systematically investigated for possible connectivity schemes and photochemical parameters. When applying a homogeneous (sequentially decaying) connectivity scheme in both the 3 and 14 ps kinetic phases, evidence for repumping of an intermediate that has an electronic ground state configuration (GSI) is taken from the dump-induced S1 formation with 620, 640 and 660 nm wavelengths and 1 and 14 ps repump delays. Evidence for repumping a GSI is also seen, for the same excitation wavelengths, when imposing a target connectivity scheme proposed in refs1,2 for the 1 ps repump d

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• Journal article
  Bolanos-Garcia VM, Lischetti T, Matak-Vinkovic D, Cota E, Simpson PJ, Chirgadze DY, Spring DR, Robinson CV, Nilsson J, Blundell TLet al., 2011,
  , STRUCTURE, Vol: 19, Pages: 1691-1700, ISSN: 0969-2126
  • Cite
  • Citations: 64
• Journal article
  Briegel A, Beeby M, Thanbichler M, Jensen GJet al., 2011,

  Activated chemoreceptor arrays remain intact and hexagonally packed

  , Mol. Microbiol., Vol: 82, Pages: 748-757
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• Journal article
  Lou H, Chen M, Black SS, Bushell SR, Ceccarelli M, Mach T, Beis K, Low AS, Bamford VA, Booth IR, Bayley H, Naismith JHet al., 2011,
  , PLOS ONE, Vol: 6, ISSN: 1932-6203
  • Cite
  • Citations: 105
• Journal article
  Boudjemline A, Saridakis E, Swann MJ, Govada L, Mavridis IM, Chayen NEet al., 2011,
  , ANALYTICAL CHEMISTRY, Vol: 83, Pages: 7881-7887, ISSN: 0003-2700
  • Cite
  • Citations: 13
• Journal article
  Yu X-J, Liu M, Matthews S, Holden DWet al., 2011,
  , JOURNAL OF BIOLOGICAL CHEMISTRY, Vol: 286, Pages: 36098-36107
  • Cite
  • Citations: 33
• Journal article
  Sheppard C, Camara B, Shadrin A, Akulenko N, Liu M, Baldwin G, Severinov K, Cota E, Matthews S, Wigneshweraraj SRet al., 2011,
  , JOURNAL OF MOLECULAR BIOLOGY, Vol: 412, Pages: 832-841, ISSN: 0022-2836
  • Cite
  • Citations: 3
• Journal article
  Hare S, Smith SJ, Metifiot M, Jaxa-Chamiec A, Pommier Y, Hughes SH, Cherepanov Pet al., 2011,
  , MOLECULAR PHARMACOLOGY, Vol: 80, Pages: 565-572, ISSN: 0026-895X
  • Cite
  • Citations: 208
• Journal article
  Shaw RK, Lasa I, Garcia BM, Pallen MJ, Hinton JCD, Berger CN, Frankel Get al., 2011,
  , ENVIRONMENTAL MICROBIOLOGY REPORTS, Vol: 3, Pages: 569-573, ISSN: 1758-2229
  • Cite
  • Citations: 23
• Journal article
  Parambil JV, Schaepertoens M, Williams DR, Heng JYYet al., 2011,
  , CRYSTAL GROWTH & DESIGN, Vol: 11, Pages: 4353-4359, ISSN: 1528-7483
  • Cite
  • Citations: 46
• Journal article
  Muangman S, Korbsrisate S, Muangsombut V, Srinon V, Adler NL, Schroeder GN, Frankel G, Galyov EEet al., 2011,
  , FEMS MICROBIOLOGY LETTERS, Vol: 323, Pages: 75-82, ISSN: 0378-1097
  • Cite
  • Citations: 14
• Journal article
  Woermann ME, Reichmann NT, Malone CL, Horswill AR, Gruendling Aet al., 2011,
  , JOURNAL OF BACTERIOLOGY, Vol: 193, Pages: 5279-5291, ISSN: 0021-9193
  • Cite
  • Citations: 83
• Book chapter
  Hare S, Engelman A, Cherepanov P, 2011,

  HIV-1 Integrase: Mechanism and Inhibitor Design

  , HIV-1 Integrase, Editors: Neamati, Publisher: Wiley, ISBN: 9780470184745

  This book comprehensively covers the mechanisms of action and inhibitor design for HIV-1 integrase. It serves as a resource for scientists facing challenging drug design issues and researchers in antiviral drug discovery.

  • Abstract
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• Journal article
  Salgado PS, Yan R, Taylor JD, Burchell L, Jones R, Hoyer LL, Matthews SJ, Simpson PJ, Cota Eet al., 2011,
  , PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol: 108, Pages: 15775-15779, ISSN: 0027-8424
  • Cite
  • Citations: 67
• Journal article
  Fillet S, Krell T, Morel B, Lu D, Zhang X, Ramos JLet al., 2011,
  , Proceedings of the National Academy of Sciences of USA, Vol: 37, Pages: 15372-15377
  • Cite
• Journal article
  Taylor JD, Zhou Y, Salgado PS, Patwardhan A, McGuffie M, Pape T, Grabe G, Ashman E, Constable SC, Simpson PJ, Lee W-C, Cota E, Chapman MR, Matthews SJet al., 2011,
  , STRUCTURE, Vol: 19, Pages: 1307-1316, ISSN: 0969-2126
  • Cite
  • Citations: 73
• Journal article
  Corrigan RM, Abbott JC, Burhenne H, Kaever V, Gruendling Aet al., 2011,
  , PLOS PATHOGENS, Vol: 7, ISSN: 1553-7366
  • Cite
  • Citations: 368
• Journal article
  Clements A, Smollett K, Lee SF, Hartland EL, Lowe M, Frankel Get al., 2011,
  , CELLULAR MICROBIOLOGY, Vol: 13, Pages: 1429-1439, ISSN: 1462-5814
  • Cite
  • Citations: 32
• Journal article
  Ho R, Dilworth SE, Williams DR, Heng JYYet al., 2011,
  , INDUSTRIAL & ENGINEERING CHEMISTRY RESEARCH, Vol: 50, Pages: 9642-9649, ISSN: 0888-5885
  • Cite
  • Citations: 37
• Journal article
  Stewart PDS, Kolek SA, Briggs RA, Chayen NE, Baldock PFMet al., 2011,
  , CRYSTAL GROWTH & DESIGN, Vol: 11, Pages: 3432-3441, ISSN: 1528-7483
  • Cite
  • Citations: 80
• Journal article
  Xia G, Corrigan RM, Winstel V, Goerke C, Gruendling A, Peschel Aet al., 2011,
  , JOURNAL OF BACTERIOLOGY, Vol: 193, Pages: 4006-4009, ISSN: 0021-9193
  • Cite
  • Citations: 132
• Journal article
  Kwek JW, Vakarelski IU, Ng WK, Heng JYY, Tan RBHet al., 2011,
  , COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS, Vol: 385, Pages: 206-212, ISSN: 0927-7757
  • Cite
  • Citations: 14

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